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  • Author or Editor: Alastair E. Cribb x
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Abstract

Objective—To determine whether a deficiency in systemic or local (pars intermedia) antioxidant capacity is associated with pituitary pars intermedia oxidative stress and pituitary pars intermedia dysfunction (PPID) in horses.

Sample Population—Blood samples from 20 horses with PPID and 20 healthy client-owned horses, archived paraffin-embedded adrenal gland and substantia nigra tissues from 20 horses, and pituitary gland tissue from 16 horses.

Procedures—Total glutathione, superoxide dismutase, and glutathione peroxidase activities were determined in RBCs. Accumulation of a systemic marker of oxidative stress (3-nitrotyrosine) was assessed in plasma and formalin-fixed, paraffinembedded adrenal gland and substantia nigra tissues. Local antioxidants (total and manganese superoxide dismutase, glutathione peroxidase, and total glutathione) were measured in pars intermedia tissues.

Results—No significant differences existed in systemic antioxidant enzyme activity or accumulation of 3-nitrotyrosine between horses with PPID and control horses. In pituitary gland tissues, glutathione peroxidase activity was increased in horses with oxidative stress, whereas total glutathione concentration and superoxide dismutase activity remained unchanged. There was an age-associated decrease in manganese superoxide dismutase activity in the pars intermedia.

Conclusions and Clinical Relevance—There was no evidence of systemic accumulation of oxidative stress markers or deficiencies in antioxidant capacity in horses with PPID, suggesting that these are unlikely to be major predisposing factors in the development of PPID. Manganese superoxide dismutase activity in the pars intermedia decreased significantly with increasing age. Role of an ageassociated decrease in antioxidant capacity for the pars intermedia in the development of PPID in horses warrants further investigation. (Am J Vet Res 2005;66:2065–2072)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of chronic exposure to excess dietary copper (Cu) on liver specimens from rats and the effects of dietary selenium (Se) supplementation in experimental Cu toxicosis.

Animals—60 weanling male Fischer 344 rats.

Procedure—Rats were randomly assigned to 4 groups of 15 rats each and fed 1 of the following 4 diets: high Cu (500 μg/g)/adequate Se (0.2 μg/g); high Cu (500 μg/g)/supplemented Se (2 μg/g); adequate Cu (18 μg/g)/adequate Se (0.2 μg/g); or, adequate Cu (18 μg/g)/supplemented Se (2 μg/g). Five rats per group were euthanatized after 3, 6, and 12 months, and liver specimens were obtained for histologic examination, histochemistry, metal analysis by atomic absorption spectrophotometry, measurement of glutathione peroxidase activity, and assessment of lipid peroxidation, using quantification of malondialdehyde (MDA) by the thiobarbituric acid reaction.

Results—Hepatic Cu concentration was significantly higher in rats fed high Cu diets (range, 9 to 18 μg/g of tissue [wet weight]), compared with rats receiving adequate Cu diets (4.0 to 5.7 μg/g of tissue). Rats fed high-Cu diets for 3, 6, and 12 months had mild multifocal hepatitis often surrounding necrotic foci. However, an increase in hepatic MDA content, indicative of lipid peroxidation, was not detected in these rats. Development of morphologic changes was not prevented by use of dietary Se supplementation.

Conclusion and Clinical Relevance—Long-term exposure to excess dietary Cu caused mild hepatic lesions in Fischer 344 rats. Dietary Se supplementation did not prevent hepatic damage in rats with Cu toxicosis. (Am J Vet Res 2001;62:1423–1427)

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in American Journal of Veterinary Research

Abstract

Objective—To investigate effects of sample handling, storage, and collection time and season on plasma α-melanocyte-stimulating hormone (α-MSH) concentration in healthy equids.

Animals—11 healthy Standardbreds and 13 healthy semiferal ponies.

Procedure—Plasma α-MSH concentration was measured by use of radioimmunoassay. Effects of delayed processing were accessed by comparing α-MSH concentrations in plasma immediately separated with that of plasma obtained from blood samples that were stored at 4oC for 8 or 48 hours before plasma was separated. Effects of suboptimal handling were accessed by comparing α-MSH concentrations in plasma immediately stored at -80°C with plasma that was stored at 25°C for 24 hours, 4oC for 48 hours or 7 days, and –20°C for 30 days prior to freezing at –80°C. Plasma α-MSH concentrations were compared among blood samples collected at 8:00 AM, 12 noon, and 4:00 PM. Plasma α-MSH concentrations were compared among blood samples collected in January, March, April, June, September, and November from horses and in September and May from ponies.

Results—Storage of blood samples at 4°C for 48 hours before plasma was separated and storage of plasma samples at 4°C for 7 days prior to freezing at –80°C resulted in significant decreases in plasma α-MSH concentrations. A significantly greater plasma α-MSH concentration was found in September in ponies (11-fold) and horses (2-fold), compared with plasma α-MSH concentrations in spring.

Conclusions and Clinical Relevance—Handling and storage conditions minimally affected plasma α-MSH concentrations. Seasonal variation in plasma α-MSH concentrations must be considered when evaluating pituitary pars intermedia dysfunction in equids. (Am J Vet Res 2004;65:1463–1468)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate concordance among veterinary pathologists in the assessment of histologic findings in the pars intermedia of pituitary gland sections from aged horses with mild signs suggestive of pituitary pars intermedia dysfunction (PPID).

Sample Population—10 pituitary glands from aged horses.

Procedure—7 pathologists were provided with signalment, clinical signs, and a single H&E-stained pituitary gland section from 10 aged horses with mild signs suggestive of PPID. Pathologists described histologic findings for each section and stated whether findings were consistent with PPID. Agreement among pathologists and with antemortem diagnostic test results was calculated.

Results—Overall, only fair agreement was found among the pathologists as to which horses had histologic findings consistent with disease (mean ± SE kappa value, 0.34 ± 0.069). Interpretation of individual sections varied, with minimal agreement (4 or 5/7 pathologists) for 5 of 10 sections evaluated. Postmortem assessment was in agreement with an antemortem endocrine diagnostic test result 79% of the time.

Conclusions and Clinical Relevance—Validation of antemortem diagnostic testing for PPID in horses often relies on the results of postmortem histologic evaluation. The lack of consensus in histologic interpretation of pituitary glands from aged horses with mild clinical signs in our study indicates that postmortem histologic evaluation of pituitary glands is an inappropriate standard in validation of antemortem diagnostic tests for detection of early PPID. Caution should be used when interpreting diagnostic test results in horses in which early PPID is suspected. (Am J Vet Res 2005;66:2055–2059)

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in American Journal of Veterinary Research

Abstract

OBJECTIVE

To assess drug-drug interactions between cannabidiol (CBD) and phenobarbital (PB) when simultaneously administered to healthy dogs.

ANIMALS

9 healthy, purpose bred Beagles.

PROCEDURES

A 3-phase prospective, randomized pharmacokinetic (PK) interaction study of CBD and PB was performed as follows: phase 1, CBD PK determination and evaluation of CBD tolerability by 3 single-dose CBD (5 mg/kg, 10 mg/kg, and 20 mg/kg) protocols followed by 2-week CBD dosing; phase 2, a single-dose, 3-way, crossover PK study of CBD (10 mg/kg), PB (4 mg/kg), or CBD (10 mg/kg) administration plus PB (4 mg/kg); and phase 3, evaluation of chronic PB (4 mg/kg, q 30 d) administration followed by single-dose CBD (10 mg/kg) PK study.

RESULTS

Although there were variations in CBD PK variables in dogs receiving CBD alone or in conjunction with PB, significance differences in CBD PK variables were not found. No significant difference was observed in PB PK variables of dogs receiving PB alone or with CBD. During chronic CBD administration, mild gastrointestinal signs were observed in 5 dogs. At daily CBD doses of 10 to 20 mg/kg/d, hypoxia was observed in 5 dogs and increased serum alkaline phosphatase (ALP) activities (range, 301 to 978 U/L) was observed in 4 dogs. A significant increase in ALP activity was observed with chronic administration of CBD during phase 1 between day 0 and day 14.

CONCLUSIONS AND CLINICAL RELEVANCE

No significant PK interactions were found between CBD and PB. Dose escalation of CBD or adjustment of PB in dogs is not recommended on the basis of findings of this study.

Free access
in American Journal of Veterinary Research